Citations

Abstract The genetics of peripheral T-cell lymphomas are poorly understood. The most well-characterized abnormalities are translocations involving ALK, occurring in approximately half of anaplastic large cell lymphomas (ALCLs). To gain insight into the genetics of ALCLs lacking ALK translocations, we combined mate-pair DNA library construction, massively parallel (“Next Generation”) sequencing, and a novel bioinformatic algorithm. We identified a balanced translocation disrupting the DUSP22 phosphatase gene on 6p25.3 and adjoining the FRA7H fragile site on 7q32.3 in a systemic ALK-negative ALCL. Using fluorescence in situ hybridization, we demonstrated that the t(6;7)(p25.3;q32.3) was recurrent in ALK-negative ALCLs. Furthermore, t(6;7)(p25.3;q32.3) was associated with down-regulation of DUSP22 and up-regulation of MIR29 microRNAs on 7q32.3. These findings represent the first recurrent translocation reported in ALK-negative ALCL and highlight the utility of massively parallel genomic sequencing to discover novel translocations in lymphoma and other cancers.

Abstract Long-term outcomes and hence the role of adjuvant therapy in patients with small (≤1 cm), node-negative breast cancer remain unclear. This study's objective was to evaluate whether human epidermal growth factor receptor (HER)-2 status is an independent, poor prognostic marker in patients with these tumors and to identify a subgroup of patients with these small tumors who might benefit from adjuvant systemic therapy. All patients with a diagnosis of a node-negative breast tumor measuring ≤1 cm and available HER-2 test results between January 1, 2001, and December 31, 2005, at the three Mayo Clinic sites were identified. Clinicopathologic data were compared in three groups: HER-2−, HER-2+, and triple-negative (TN) tumors. Of the 421 tumors identified, 364 (86.5%) were HER-2−, 28 (6.7%) were HER-2+, and 29 (6.9%) were TN. The median follow-up time was 1,015 days (range, 1–2,549 days). Groups were balanced in terms of patient age and tumor histology. Eleven patients with HER-2− tumors (3.0%), seven with HER-2+ tumors (25.0%), and eight with TN tumors (27.6%) received adjuvant chemotherapy. Follow-up data were available for 357, 28, and 28 patients in the three groups, respectively. Death rates in the three groups were 6.4% (23 of 357) (one recurrence-related death), 0% (0 of 28), and 7.1% (2 of 28) (one recurrence-related death), respectively. During follow-up, the tumor recurred in nine patients: four were HER-2− tumors (1.1%), two were HER-2+ tumors (7.1%), and three were TN tumors (10.7%). Patients with small, node-negative breast tumors have an excellent prognosis, but HER-2+ and TN tumors appear to have a higher recurrence rate, warranting consideration for broad use and optimization of systemic adjuvant treatments.

Abnormal expression of genes for energy regulation in Parkinson’s disease patients identifies a master regulator as a possible therapeutic target for early intervention.

Purpose The goal of this study was to determine the frequency and clinical features of early treatment failure during induction chemotherapy before protocol radiation therapy for children with intermediate-risk rhabdomyosarcoma (RMS). Patients and Methods Patients with intermediate-risk RMS enrolled onto the Intergroup Rhabdomyosarcoma Study-IV and the Children's Oncology Group D9803 study were reviewed for an early treatment failure. Early failure was defined as failure caused by progressive disease, death as a result of progressive disease, or death as a result of other causes occurring fewer than 120 days from study entry. Patients with parameningeal site RMS with high-risk features who received radiation therapy at week 1 were excluded from analysis. Overall survival (OS) was estimated using the Kaplan-Meier method. Fisher's exact test was used to compare differences between groups. Cumulative incidence of progression was estimated. Results Of 916 patients, 20 (2.2%) were found to have an early disease progression and did not receive planned protocol radiotherapy. Three additional early failures resulted from treatment-related death without progression. Median time to failure was 48 days (range, 7 to 106 days). Nineteen (95%) of the 20 patients experienced progression at their primary site. Five-year OS was 32% (95% CI, 12% to 54%) for patients experiencing an early progression. Conclusion A small proportion of patients with intermediate-risk RMS suffer an early failure as a result of early progression (2.2%) or treatment-related mortality (0.3%). The majority of patients with early progression had a local failure. Earlier radiotherapy could potentially improve outcome by preventing early local progression.

Purpose. To gather consumer input about approaches to providing energy composition information for foods on fast-food restaurant menus. Design. We asked a subset of individuals (n = 150) in an experimental study about the influence of nutrition labeling on fast-food meal choices to evaluate calorie information on mock fast-food menus in various formats. Setting. Three community sites in the Minneapolis-St. Paul, Minnesota, metropolitan area. Subjects. Adolescents and adults who ate fast food at least once per week were recruited. Measures. Via a series of open- and close-ended questions, participants gave feedback about several formats for providing energy composition information for foods on fast-food restaurant menus. Analysis. Means and frequencies were calculated, and χ 2 tests were conducted. Results. When asked to compare a menu that provided calorie information for each menu item with a menu that provided the number of minutes of running that would be required to burn the calories contained in each menu item, 71.0% of participants preferred the calorie information over the physical activity information. Participants also compared two approaches to providing caloric reference information on the menu (average daily calorie needs per day vs. per meal), and 61.3% preferred the calorie needs—per-meal format. Conclusion. Our results may be useful in designing approaches to providing energy composition information for foods on fast-food restaurant menus.

The Alzheimer's Disease Neuroimaging Initiative (ADNI) beginning in October 2004, is a 6‐year research project that studies changes of cognition, function, brain structure and function, and biomarkers in elderly controls, subjects with mild cognitive impairment, and subjects with Alzheimer's disease (AD). A major goal is to determine and validate MRI, PET images, and cerebrospinal fluid (CSF)/blood biomarkers as predictors and outcomes for use in clinical trials of AD treatments. Structural MRI, FDG PET, C‐11 Pittsburgh compound B (PIB) PET, CSF measurements of amyloid β (Aβ) and species of tau, with clinical/cognitive measurements were performed on elderly controls, subjects with mild cognitive impairment, and subjects with AD. Structural MRI shows high rates of brain atrophy, and has high statistical power for determining treatment effects. FDG PET, C‐11 Pittsburgh compound B PET, and CSF measurements of Aβ and tau were significant predictors of cognitive decline and brain atrophy. All data are available at UCLA/LONI/ADNI, without embargo. ADNI‐like projects started in Australia, Europe, Japan, and Korea. ADNI provides significant new information concerning the progression of AD.

The Clinical Core of the Alzheimer's Disease Neuroimaging Initiative (ADNI) has provided clinical, operational, and data management support to ADNI since its inception. This article reviews the activities and accomplishments of the core in support of ADNI aims. These include the enrollment and follow‐up of more than 800 subjects in the three original cohorts: healthy controls, amnestic mild cognitive impairment (now referred to as late MCI, or LMCI), and mild Alzheimer's disease (AD) in the first phase of ADNI (ADNI 1), with baseline longitudinal, clinical, and cognitive assessments. These data, when combined with genetic, neuroimaging, and cerebrospinal fluid measures, have provided important insights into the neurobiology of the AD spectrum. Furthermore, these data have facilitated the development of novel clinical trial designs. ADNI has recently been extended with funding from an NIH Grand Opportunities (GO) award, and the new ADNI GO phase has been launched; this includes the enrollment of a new cohort, called early MCI, with milder episodic memory impairment than the LMCI group. An application for a further 5 years of ADNI funding (ADNI 2) was recently submitted. This funding would support ongoing follow‐up of the original ADNI 1 and ADNI GO cohorts, as well as additional recruitment into all categories. The resulting data would provide valuable data on the earliest stages of AD, and support the development of interventions in these critically important populations.

Stiff skin syndrome, an autosomal dominant congenital form of scleroderma, is caused by mutations in the domain of fibrillin-1 that mediates integrin binding.